Method for producing polyoxyalkylene glycols

ABSTRACT

The present invention relates to a process for preparing polyoxyalkylene glycol of high purity and having a low color number from the corresponding alkylene glycol and a starter in the presence of a basic catalyst, wherein a reducing agent is present in the polymerization.

The present invention relates to a process for preparing polyoxyalkyleneglycols by polymerizing the corresponding alkylene glycols in thepresence of a reducing agent. This results in a polyoxyalkylene glycol,especially a polyethylene glycol, of high purity and having low colornumbers.

One route to the preparation of polyoxyalkylene glycols is thepolymerization of the corresponding alkylene oxides using basiccatalysts, for example hydroxides or alkoxides of the alkali metals andalkaline earth metals. An alcohol is also added as a starter, and thenaddition reaction of the alkylene oxide to the starter takes place.

Examples of polyoxyalkylene glycols are polyethylene glycol PEG,polypropylene glycol PPG and polybutylene glycol PBG, which are preparedfrom ethylene oxide EO, propylene oxide PO and butylene oxide BOrespectively. Also known are mixed polymers of EO, PO and/or BO, forexample EO with PO. The mixed polymers may be random polymers or blockcopolymers.

Polyoxyalkylene glycols have highly varied fields of application. Inmany, high requirements are placed on the purity and color number of thepolyoxyalkylene glycol, for instance in products which are taken byhumans, for example in foods and pharmaceutical products. Thepolyoxyalkylene glycol most frequently used in these fields is PEG.

The requirements on PEG used in pharmaceutical products are defined inhighly varied pharmacopoeias, for example the Deutsche Arzneimittelbuch[German Pharmacopoeia] DAB, the US Pharmacopoeia USP and the EuropeanPharmacopoeia EUP. For instance, according to USP, the PEG has to becolorless, and according to EUP, the maximum color number as a 25%solution in water is 20 APHA. Examples of further requirements are amaximum water content of 0.2%, a maximum content of monoethylene glycoland diethylene glycol together of 0.25%, a maximum content of sulfateash of 0.1% and a maximum aldehyde content (expressed as HCHO) of 30ppm.

To industrially prepare polyoxyalkylene glycols, in particular PEG,which meet the high requirements in the foods and pharmaceuticalssector, the starting products, including polyoxyalkylene glycols, aregenerally of high purity. This requires a costly and inconvenientprepurification of the reactants and is therefore costly. There existonly a few patent applications relating to the preparation ofpolyoxyalkylene glycols from alkylene glycols of technical gradequality.

EP-A 1 245 608 describes the use of triethylene glycol TEG for thepreparation of polyethylene glycols to achieve a low content ofmonoethylene glycol MEG and diethylene glycol DEG. This results in a PEGhaving low MEG and DEG contents, although no information is given withregards to further requirements. In particular, not even the colornumber of the products obtained is mentioned.

RO-A 62314 describes the preparation of tetraethylene glycol from TEGand EO under base catalysis. For purification, the product has to bedistilled.

JP-A 53 046 907 describes the catalytic hydrogenation of polyalkyleneoxides to reduce the color number in the products.

It can be stated that hitherto there exist only a few processes whichcan be used on the industrial scale and allow polyoxyalkylene glycols ofhigh purity to be prepared from alkylene glycols of technical gradequality. These processes frequently deliver a certain polyoxyalkyleneglycol in the desired high purity, but other polyoxyalkylene glycols arenot obtainable in the desired purities, if at all.

It is an object of the present invention to provide a process forpreparing polyoxyalkylene glycols, in particular PEG, which starts fromalkylene glycols of technical grade purity and deliver the desiredproducts in qualities which satisfy the high requirements on color andpurity. The process should be usable universally. The polyoxyalkyleneglycols or the PEG should preferably satisfy the requirements in thefoods and pharmaceutical industry. In particular, the requirements laiddown in different pharmacopoeias should be fulfilled.

We have found that this object is achieved by a process for preparingpolyoxyalkylene glycol of high purity and having a low color number fromthe corresponding alkylene oxide and a starter in the presence of abasic catalyst, wherein a reducing agent is present in thepolymerization.

The polyoxyalkylene glycol is preferably PEG.

It has been found that the presence of a reducing compound during thepolymerization reaction allows polyoxyalkylene glycols of high purityand low color number to be obtained.

Preference is given to adding the reducing agent before thepolymerization. However, it can also be added during the polymerization.

It is possible to use the customary reducing agents which are known tothose skilled in the art. Examples include complex hydrides, for exampleborohydrides and aluminohydrides, preferably LiAlH4, NaBH4, LiBH4 andKBH4, BH3, alkylboranes and hydrogen in combination with hydrogenationcatalysts known to those skilled in the art and also mixtures of thereducing agents mentioned. Greater preference is given to borohydrides,particular preference to KBH4 or NaBH4 and mixtures thereof.

The reducing agent is used in amounts of from 0.002 to 0.06% by weight,preferably from 0.002 to 0.02% by weight, in particular from 0.004 to0.02% by weight. It can be used in the form of a solid or as a solutionor suspension in a suitable solvent. Suitable solvents are known tothose skilled in the art, and examples include the alkali-stabilizedsolution, tertiary alcohols, secondary alcohols, for exampleisopropanol, or else primary alcohols such as methanol and ethanol. Thealcohol used as a starter can also serve as the solvent.

Preference is given to adding the reducing agent in the form of asolution.

According to the invention, highly differing starters can be used, andtheir use depends on the polyoxyalkylene glycol to be obtained. Examplesof suitable starters include monoethylene glycol MEG, diethylene glycolDEG, triethylene glycol TEG, monopropylene glycol MPG, dipropyleneglycol DPG, tripropylene glycol TPG, monobutylene glycol and dibutyleneglycol.

Suitable basic catalysts are known to those skilled in the art and aregenerally selected from hydroxides and alkoxides of the alkali metalsand alkaline earth metals. It is added in an amount of from 0.001 to 5%by weight, preferably from 0.01 to 1% by weight. According to theinvention, the catalysts are generally used in combination with thereducing agent, and can be added in form of a mixture with the starteror reducing agent or separately to the reaction mixture to be reacted.

As an alternative to the separate use of reducing agent and catalyst, itis possible to use strongly basic reducing agents which generatealkoxides in situ. Examples of such basic reducing agents includeLiAlH4, KAlH4 and NaBH4 in alkaline-stabilized aqueous solution,preferably with NaOH or KOH.

The reaction of the starter with alkylene oxide is generally carried outin such a way that starter and catalyst and/or the basic reducing agentare mixed before the addition of alkylene oxide, optionally dewateredand brought to the reaction temperature above 80° C. The alkylene oxideis then added. Once the reaction abates, the mixture is cooled anddrained from the reactor. Preference is given to carrying out thereaction in a temperature range between 105 and 180° C., more preferablybetween 115 and 160° C.

It is suspected that the high color numbers of polyoxyalkylene glycolswhich result when starters of technical grade quality are polymerizedare caused by the presence of aldehydes. As the examples show, the highcolor numbers of the polyoxyalkylene glycols obtained by polymerizationof starters of technical grade quality correlate with the amount of thecarbonyl function in the starter. The addition of the reducing agentsused according to the invention reduces these carbonyl functions(aldehydes and ketones) and thus achieves low color numbers.

Preference is given to using the present invention to preparepolyethylene glycol PEG of high purity and low color number from starterof technical grade quality. Greater preference is given to the starterused being triethylene glycol TEG. In such a case, a PEG is obtainedwhich has not only a low color number but also a small amount of MEG andDEG and is therefore suitable in principle for use in foods andpharmaceutical products.

In particular, the process according to the invention is used, in orderto prepare PEG from ethylene oxide using TEG as the starter, said PEGhaving a molecular weight of from 150 to 500 mol/g, preferably from 190to 300 mol/g, in particular from 190 to 250 mol/g. Industrial scaleprocesses which deliver PEG having a molecular weight of ≦500 g/mol andof the quality achieved in accordance with the invention from startersof technical grade quality do not yet exist.

The color number achieved by the process according to the inventiondepends on the purity of the starting products and also on the amount ofreducing agent. When preparing PEG, the process according to theinvention allows the use of starters having carbonyl contents of >25ppm. According to the invention, it is possible to achieve color numbersof <20 APHA, which means that an appropriate PEG achieves therequirements of the European Pharmacopoeia. Adjustment of the reactionconditions and of the starting products selected also allows PEGqualities according to USP to be obtained which are colorless. This isgenerally the case for color numbers of <10 APHA.

The invention is illustrated by the examples which follow.

EXAMPLE 1 (COMPARATIVE)

900 g of triethylene glycol (carbonyl content as acetaldehyde 400 ppm)are charged into a pressure vessel with 1.2 g of KOH. This mixture isthen reacted with 300 g of ethylene oxide at from 120 to 130° C. Oncompletion of the reaction, the product is discharged under nitrogen andanalyzed: Hazen color number 354 APHA.

EXAMPLE 2 (COMPARATIVE)

300 g of TEG (carbonyl content as acetaldehyde 25 ppm) are charged intoa pressure vessel with 1.33 g of 30% sodium methoxide in methanol.Methanol is removed at 80° C. under reduced pressure (20 mbar). Themixture is then reacted with 100.3 g of ethylene oxide at from 120 to130° C. On completion of the reaction, the product is discharged undernitrogen and analyzed: Hazen color number 22 APHA.

EXAMPLE 3

300 g of TEG (carbonyl content as acetaldehyde 4000 ppm) are chargedinto a pressure vessel with 1.50 g of borol solution (aqueous solutionof approx. 12% of NaBH4 and approx. 40% of NaOH). Water is removed at80° C. under reduced pressure (20 mbar). The mixture is then reactedwith 100.3 g of ethylene oxide at from 120 to 130° C. On completion ofthe reaction, the product is discharged under nitrogen and analyzed:Hazen color number 12 APHA.

EXAMPLE 4

600 g of TEG (carbonyl content as acetaldehyde 75 ppm) are charged intoa pressure vessel with 0.72 g of borol solution. Water is removed at100° C. under reduced pressure (20 mbar). The mixture is then reactedwith 100.3 g of ethylene oxide at from 120 to 130° C. On completion ofthe reaction, the product is discharged under nitrogen and analyzed:Hazen color number 6 APHA. GC analysis: MEG<0.05%, DEG<0.05%, sulfateash 0.08%, appearance: clear, viscosity: 4.43 mm2/s (98.9° C.), OHnumber: 557 mg of KOH/g.

EXAMPLE 5

300 g of TEG (carbonyl content as acetaldehyde 72 ppm) are charged intoa pressure vessel with 0.09 g of borol solution. Water is removed at100° C. under reduced pressure (5 mbar). The mixture is then reactedwith 100.3 g of ethylene oxide at from 120 to 130° C. On completion ofthe reaction, the product is discharged under nitrogen and analyzed:Hazen color number 2 APHA.

EXAMPLE 6

300 g of TEG (carbonyl content as acetaldehyde 72 ppm) are charged intoa pressure vessel with 0.18 g of borol solution. Water is removed at100° C. under reduced pressure (5 mbar). The mixture is then reactedwith 100.3 g of ethylene oxide at from 145 to 155° C. On completion ofthe reaction, the product is discharged under nitrogen and analyzed:Hazen color number 6 APHA.

All color numbers mentioned relate to a 25% solution of the products inwater.

1-14. (canceled)
 15. A process for preparing polyoxyalkylene glycol ofhigh purity and having a low color number, comprising reacting thecorresponding alkylene oxide and a starter, in the presence of a basiccatalyst, and wherein a reducing agent is present in the polymerization.16. The process as claimed in claim 15, wherein the starter is oftechnical grade quality.
 17. The process as claimed in claim 15, whereinthe reducing agent is added before, or at the beginning of, thepolymerization.
 18. The process as claimed in claim 17, wherein thereducing agent is added before the polymerization.
 19. The process asclaimed in claim 15, wherein the reducing agent is selected from complexhydrides, BH3, alkylboranes and hydrogen in combination withhydrogenation catalysts known to those skilled in the art, or mixturesthereof.
 20. The process as claimed in claim 19, wherein the reducingagent is selected from borohydrides or aluminohydrides.
 21. The processas claimed in claim 20, wherein the reducing agent is selected fromLiAlH4, NaBH4, LiBH4 or KBH4.
 22. A process as claimed in claim 15,wherein the amount of reducing agent is from 0.002 to 0.06% by weight.23. The process as claimed in claim 22, wherein the amount of reducingagent is from 0.002 to 0.02% by weight.
 24. The process as claimed inclaim 22, wherein the amount of reducing agents is from 0.004 to 0.02%by weight.
 25. The process as claimed in claim 15, wherein the basiccatalyst is selected from hydroxides or alkoxides of the alkali metalsand alkaline earth metals.
 26. The process as claimed in claim 15,wherein the basic catalyst is added in an amount of from 0.001 to 5% byweight.
 27. The process as claimed in claim 26, wherein the basiccatalyst is added in an amount of from 0.01 to 1% by weight.
 28. Theprocess as claimed in claim 15, wherein the reducing agent includes anamount of base, or has basic properties itself.
 29. The process asclaimed in claim 28, wherein the reducing agent is selected from KBH4 orNaBH4 in alkali-stabilized aqueous solution.
 30. The process as claimedin claim 28, wherein the reducing agent is selected from KBH4 or NaBH4in alkali-stabilized aqueous solution with NaOH or KOH.
 31. The processas claimed in claim 15, wherein the starter is selected from the groupconsisting of monoethylene glycol MEG, diethylene glycol DEG,triethylene glycol TEG, monopropylene glycol MPG, dipropylene glycolDPG, tripropylene glycol TPG, monobutylene glycol and dibutylene glycol.32. The process as claimed in claim 15, wherein the polyoxyalkyleneglycol is polyethylene glycol.
 33. The process as claimed in claim 32,wherein the starter is triethylene glycol.
 34. The process as claimed inclaim 33, wherein the polyethylene glycol obtained, has a molecularweight of from 150 to 500 g/mol.
 35. The process as claimed in claim 33,wherein the polyethylene glycol obtained, has a molecular weight of from190 to 300 g/mol.
 36. The process as claimed in claim 33, wherein thepolyethylene glycol obtained, has a molecular weight of from 190 to 250g/mol.
 37. The process as claimed in claim 33, wherein the starter hascarbonyl contents of >25 ppm.
 38. A method for producing food products,comprising adding the polyethylene glycol obtained by the process ofclaim 32 to a food product.
 39. A method for producing pharmaceuticalproducts, comprising adding the polyethylene glycol obtained by theprocess of claim 32 to a pharmaceutical product.